Heart Rhythm After Intravenous Methylprednisolone Administration

May 13, 2020 updated by: Piotr Miskiewicz, Medical University of Warsaw

Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy

High doses of intravenous (iv.) glucocorticoids (GCs) are commonly used as a treatment for many autoimmune and inflammatory disorders. According to the European Group on Graves' Orbitopathy (EUGOGO) guidelines, intravenous methylprednisolone (IVMP) is an accepted first-line agent for active, moderate-to-severe and very severe Graves' orbitopathy (GO). This treatment is proven to be more efficient and safer than oral GCs. However, some patients may experience adverse cardiovascular effects during the administration of iv. GCs, which in rare cases may even be fatal. There are limited data, mostly obtained from case reports, reporting the occurrence of cardiac arrhythmias, acute myocardial infarction or heart failure. Increased heart rhythm (HR) has drawn attention of researchers as a possible adverse effect correlated with IVMP. During this study, investigators performed 72-hours of Holter ECG and ambulatory blood pressure monitoring (ABPM) to evaluate the impact of IVMP on patients with moderate-to-severe GO, concerning HR and blood pressure (BP) changes. In order to elucidate possible mechanism of observed changes, researchers investigated the level of potassium in serum and urine and catecholamines (epinephrine, norepinephrine) in serum. All patients were treated routinely according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines active, moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The clinical status of patients was evaluated before each pulse, including blood pressure monitoring, glucose level monitoring and symptoms of infection. HR and BP was measured continuously for 3 consecutive days (the day before, the day of IVMP and the day after IVMP) during 1st, 6th and 12th IVMP pulse, using 24-hour Holter ECG and ABMP. Serum laboratory tests for potassium, epinephrine and norepinephrine were measured 3 times the day before and the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP. Additionally, urine samples for potassium were collected 5 times the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO

Description

Inclusion Criteria:

  • active, moderate-to-severe GO according to EUGOGO classification
  • euthyroidism
  • completion of 12 IVMP pulses.

Exclusion Criteria:

  • cardiovascular morbidity (such as chronic heart failure and/or coronary heart disease)
  • uncontrolled hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg)
  • contraindications to IVMP therapy
  • previous GCs treatment in the last 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
active, moderate-to-severe GO
Each participant received IVMP according to EUGOGO recommendations (cumulative dose of methylprednisolone 4.5 g, treatment duration 12 weeks in single weekly intravenous pulses, first 6 weeks 0.5g of IVMP, next 6 weeks 0.25g of IVMP).
Drug: Intravenous Methylprednisolone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
24-hour Holter ECG Monitoring - 1st pulse mean HR
Time Frame: 72 hours
Analysis of changes in mean HR between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
72 hours
24-hour Holter ECG Monitoring - 6th pulse mean HR
Time Frame: 72 hours
Analysis of changes in mean HR between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP
72 hours
24-hour Holter ECG Monitoring - 12th mean HR
Time Frame: 72 hours
Analysis of changes in mean HR between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP
72 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Serum potassium levels Day 0 - Day 1
Time Frame: 48 hours
Change in value of potassium between day before and day of 1st pulse of IVMP
48 hours
Serum epinephrine levels Day 0 - Day 1
Time Frame: 48 hours
Change in value of epinephrine between day before and day of 1st pulse of IVMP
48 hours
Serum norepinephrine levels Day 0 - Day 1
Time Frame: 48 hours
Change in value of norepinephrine between day before and day of 1st pulse of IVMP
48 hours
Urine potassium levels Day 0
Time Frame: 24 hours
Change in value of potassium during the day of 1st pulse of IVMP
24 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP
Time Frame: 72 hours
Analysis of changes in mean BP between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP
Time Frame: 72 hours
Analysis of changes in mean BP between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP
72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP
Time Frame: 72 hours
Analysis of changes in mean BP between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP
72 hours

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Serum potassium levels Day 0 - Day 7
Time Frame: 7 days
Change in value of potassium between day before and sixth day after 1st pulse of IVMP
7 days
Serum potassium levels Day 0 - Day 2
Time Frame: 72 hours
Change in value of potassium between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
72 hours
Serum epinephrine levels Day 0 - Day 7
Time Frame: 7 days
Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP
7 days
Serum epinephrine levels Day 0 - Day 2
Time Frame: 72 hours
Change in value of epinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
72 hours
Serum norepinephrine levels Day 0 - Day 7
Time Frame: 7 days
Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP
7 days
Serum norepinephrine levels Day 0 - Day 2
Time Frame: 72 hours
Change in value of norepinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
72 hours
Urine potassium levels Day 1- Day 2
Time Frame: 48 hours
Change in value of epinephrine between day of 1st IVMP and day after 1st pulse of IVMP
48 hours
Urine potassium levels Day 3 - Day 7
Time Frame: 5 days
Change in value of epinephrine between second and sixth day after 1st IVMP
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Warsaw

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 20, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IVMPheartrate

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The collected data will be shared in a publication. It includes all laboratory results from all points of evaluation, results of 72-hour Holter ECG and 72-hour ABPM.

IPD Sharing Time Frame

The results of the study will be published in 2020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings